Gastric cancer is one of the most common cancers and the second leading cause of cancer‑associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c‑Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T‑cell lymphoma...

Multiple myeloma (MM) remains as an incurable disease, despite recent substantial improvements in treatment. Therefore, development of novel biomarkers for risk stratification and new therapeutic targets are imperative. One of the emerging treatments for MM is the immune checkpoint blockades. V-set Ig domain-containing 4 (VSIG4) is a lately studied B7-related immune checkpoint modulator. We assessed the VSIG4 expression in patients with MM and its prognostic impact. We analyzed 81 bone marrow and 66 extramedullary biopsy samples of MM patients using immunohistochemistry...

On November 19, 2015, a marketing authorization valid through the European Union was issued for carfilzomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.In a phase III trial in patients with relapsed MM, median progression-free survival (PFS) for patients treated with carfilzomib in combination with lenalidomide and dexamethasone (CRd) was 26.3 months versus 17.6 months for those receiving lenalidomide and dexamethasone alone (hazard ratio = 0...

The deubiquitinase USP5 stabilizes c-Maf, a key transcription factor in multiple myeloma (MM), but the mechanisms and significance are unclear. In the present study, USP5 was found to interact with c-Maf and prevented it from degradation by decreasing its polyubiquitination level. Specifically, the 308th and 347th lysine residues in c-Maf were critical for USP5-mediated deubiquitination and stability. There are five key domains in the USP5 protein and subsequent studies revealed that the cryptic ZnF domain and the C-box domain interacted with c-Maf but the UBA1/UBA2 domain partly increased its stability...

BACKGROUND: Notable progress has been made in chemo- and immunotherapy of B-cell lymphomas, but less in the treatment of T-cell lymphomas. OBJECTIVE: Histone deacetylases inhibitors are a potentially useful therapeutic mean, as an epigenetic dysregulation is present in lymphomas, and especially in T-cell types. We aimed to study the progress made in this area. METHOD: A minireview was achieved using the articles published in PubMed in the last two years and the new patents made in this field...

Proliferation and programmed cell death are tightly correlated with the ubiquitin-proteasome system (UPS). Alterations in the UPS may be implicated in pathological conditions such as the proteasome over-activity in cancer cells. Mounting evidence indicates that many types of actively proliferating malignant cells are more sensitive to proteasome inhibition than normal cells, and therefore UPS inhibitors are actively pursued as anticancer agents. The approval of the proteasome inhibitor drug bortezomib for the treatment of myeloma and lymphoma further highlights the need for UPS inhibitors...

Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme in the de novo biosynthesis pathway of pyrimidines. Inhibition of this enzyme impedes cancer cell proliferation but the exact mechanisms of action of these inhibitors in cancer cells are poorly understood. In this study, we showed that cancer cells, namely melanoma, myeloma and lymphoma overexpressed DHODH protein and treatment with A771726 and Brequinar sodium resulted in cell cycle arrest at S-phase. Transfection with DHODH shRNA depleted DHODH protein expression and impeded the proliferation of melanoma cells...

The characteristics of the proliferation of B-cell activating factor (BAFF) and the proliferation-inducing ligand (APRIL) mRNA expression in mononuclear cell in multiple myeloma patients were detected, and the correlation was analyzed between the BAFF and APRIL concentrations in plasma and tumor burden parameters of multiple myeloma. Bone marrow samples from 60 patients with multiple myeloma and 20 healthy persons taken as controls, were collected. Bone marrow mononuclear cells (BMMCs) were harvested, and plasma was extracted...

Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T-cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR T-cells against leukemia and lymphoma has encouraged development of CAR T-cell therapies for MM...

Immunomodulatory drugs (IMiDs) are profoundly active compounds in the treatment of patients with multiple myeloma (MM). However, despite the fact that treatment with IMiDs has dramatically improved survival for patients with MM, the majority of MM patients develop IMiDs resistance over time. We have found that expression of functional cereblon is required for IMiDs' action. In addition, it has been reported that cells expressing high levels of cereblon are resistant to proteasome inhibitor, implying that patients with high levels of cereblon should be resistant to proteasome inhibitor...

BACKGROUND: In an autologous hematopoietic cell transplantation (AHCT) setting, routine cytomegalovirus (CMV) surveillance is not indicated except in high-risk situations. On the other hand, some studies reported increased CMV reactivation in AHCT setting as a result of incorporation of novel agents into treatment algorithms, such as bortezomib and rituximab. We retrospectively analyzed CMV reactivation and infection rates in patients with no high-risk features, who were treated with AHCT...

A series of 1,4-naphthoquinones (10a-10q) were synthesized and evaluated for anticancer activity. Compound 10e was identified as an inhibitor of Itch, a HECT domain-E3 ligase. In an evaluation of in vivo efficacy, 10e exhibited remarkable anticancer activity with TGI values of 98.3% and 100% at 25 mg/kg and 50 mg/kg orally daily, respectively, against human RPMI-8226 multiple myeloma xenograft. Treatment with 10e also showed a decrease of Itch level in human RPMI-8226 multiple myeloma cells. Thus 10e is a lead compound for further development of inhibitors targeting E3 ligase for treatment of multiple myeloma...

PURPOSE: Hematopoietic stem cell transplantation (HCT) is potentially curative for a number of hematologic malignancies, but is associated with high symptom burden. We conducted a randomized sham-controlled trial (RCT) to evaluate efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan followed by autologous HCT (AHCT) were randomized to receive either true or sham acupuncture once daily for 5 days starting the day after chemotherapy...

Dexamethasone is widely used in multiple myeloma (MM) for its cytotoxic effects on lymphoid cells. However, many MM patients are resistant to dexamethasone, although some can benefit from dexamethasone treatment. In this study, we noted that ω-3 polyunsaturated fatty acids (PUFAs) enhanced the dexamethasone sensitivity of MM cells by inducing cell apoptosis. q-PCR analysis revealed that miR-34a could be significantly induced by PUFAs in U266 and primary MM cells. Transfection with miR-34a antagonist or miR-34a agomir could restore or suppress the dexamethasone sensitivity in U266 cells...

The D-type cyclin (CCND)-cyclin-dependent kinase 4/6 (CDK4/6) complex has been implicated in multiple myeloma development. We investigated the biological activity of CDK4/6 inhibitor abemaciclib on cell growth and survival in three myeloma cell lines, KMS-12-PE, RPMI 8226, and IM-9. Abemaciclib inhibited myeloma cell growth in a dose-dependent manner in all cell lines, with significant differences seen at a concentration of 320 nM. Treatment with 1 μM abemaciclib increased the fraction of cells in the G0/G1 phase and decreased the fraction in the S-G2/M phases...

The C - X - C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical use, i.e. for mobilization and subsequent harvesting of hematopoietic progenitor cells and stem cell transplantation. In a pathological condition, involvement in the process of metastasis and homing of cancer cells to a protective niche has been described, making CXCR4 an attractive target for imaging and treatment of malignant diseases...

It is known that multiple myeloma (MM) cells express CD38 and that a recently developed human anti-CD38 monoclonal antibody Daratumumab mediates myeloma killing. However, the expression of CD38 and other functionally related ectoenzymes within the MM bone niche and the potential effects of Daratumumab on bone cells are still unknown. This study firstly defines by flow cytometry and immunohistochemistry the expression of CD38 by bone marrow cells in a cohort of patients with MM and indolent monoclonal gammopathies...